Ryan Spilborghs also connected and Esmil Rogers (2-0) won his second straight outing to begin the season as Colorado earned its fourth consecutive victory - all on the road.
The NL West leaders improved to 8-2, with the only two losses coming in extra innings. The Rockies, who opened 7-3 in 1995 and '97, are 5-1 away from Coors Field after going 31-50 on the road last year.
Tulowitzki, who foiled the Mets with his bat and glove in the series opener Monday night, made them pay again for pitching to him with first base open. He hit a three-run shot off Jonathon Niese (0-2) in the fifth inning to give Colorado a 4-3 lead.
The slugger also doubled and singled, meaning eight of his 11 hits this season have gone for extra bases.
Carlos Beltran and Daniel Murphy each had an RBI double for the Mets, who have dropped six of seven following a three-game winning streak.
The teams will play three games in a 24-hour span - a rainout Tuesday night forced Thursday's traditional doubleheader, which begins at 12:10 p.m.
The weather was only slightly better Wednesday, when players could see their own breath on a gloomy, misty, 49-degree night that felt more like Victorian London than New York City.
After throwing 7 1-3 strong innings to win 7-1 at Pittsburgh last Thursday, Rogers lasted 5 2-3 innings this time. He gave up three runs and seven hits before four relievers finished up.
Huston Street tossed a perfect ninth for his sixth save in six chances.
Carlos Gonzalez made a diving catch in left field to save a run in the first for the Rockies.
Seth Smith drew a one-out walk in the fifth, Jonathan Herrera singled and Gonzalez's slow groundout left runners at second and third. With first base open the Mets had a chance to walk Tulowitzki and instead face Jose Lopez with the bases loaded, but manager Terry Collins chose not to.
Tulowitzki reached for an 0-1 pitch that appeared to be outside and punched a slicing shot into the right-field corner. His fifth home run of the season, and second in the past two games at spacious Citi Field, put Colorado ahead 4-3.
The All-Star shortstop hit a two-run shot with first base open in the eighth inning Monday night, giving the Rockies a three-run cushion in a 7-6 victory. He also made an outstanding defensive play to preserve a seventh-inning tie in that game.
Spilborghs added a solo shot off Niese in the sixth, his first of the season. New York cut it to 5-4 on Angel Pagan's sacrifice fly in the seventh.
With Tulowitzki at the plate in the top of the seventh, Herrera stole second and third on consecutive pitches by Taylor Buchholz. Needing a triple for the cycle, Tulowitzki then struck out and Lopez also went down on strikes.
The Mets intentionally walked Tulowitzki with first base open in the ninth and got out of the inning unscathed.
Tulowitzki doubled in the fourth and scored on Todd Helton's single.
NOTES: Helton (stiff lower back) returned to the starting lineup. ... Rockies ace Ubaldo Jimenez was hitting 97 mph with his fastball during an extended spring training game in Arizona and remains on target to return to the rotation Monday night against San Francisco, manager Jim Tracy said. Jimenez is on the 15-day disabled list with a cut finger cuticle. ... RHP Greg Reynolds is set to start the opener for Colorado on Thursday and LHP Jorge De La Rosa will go in the second game. RHP R.A. Dickey and LHP Chris Capuano will pitch for New York. ... Mets RHP Chris Young has tendinitis in his surgically repaired arm and his next scheduled start has been pushed back two days until Sunday. New York plans to bring RHP D.J. Carrasco out of the bullpen for a spot start in Atlanta on Friday night. ... The Mets said RHP Blaine Boyer cleared waivers and elected to become a free agent.
(Copyright 2011 by The Associated Press. All Rights Reserved.)